BK病毒相关性肾病的诊治特点及相关临床因素分析

Clinical feature and analysis on the clinical related factors of BK virus associated nephropathy

目的了解BK病毒相关性肾病（BKVAN）在肾移植受者中的发病情况，观察BKVAN的病理特点。方法对1999年12月至2008年1月中山大学附属第一医院行移植肾穿刺活检的137份组织标本进行BK病毒的免疫组织化学染色，并对免疫组织化学阳性的肾组织标本及尿中脱落的肾小管上皮细胞进行透射电子显微镜检查，了解BKVAN的发病相关因素、临床表现、诊治特点及预后。应用Kaplan-Meier分析计算BKVAN患者1、3年移植肾存活率。结果137份移植肾标本中共诊断BKVAN16份（分属16例患者），占11．7％。其中3份肾组织和7份尿沉渣肾小管上皮细胞核内发现直径为35—40nm的病毒颗粒。16例BKVAN患者既往发生过急性排斥反应及使用过多／单克隆抗体者各7例，免疫抑制方案为他克莫司＋酶酚酸酯的10例，14例表现为血清肌酐升高类似急性排斥反应。4例患者在使用强效免疫抑制剂后移植肾失功能，8例患者接受减少免疫抑制剂或转换免疫抑制剂治疗后肾功能得到改善，其余4例患者免疫抑制方案未予调整最终移植肾功能恶化或失功能。BKVAN受者1、3年移植肾存活率分别为81．3％、54．2％。结论对于移植后肾功能减退，尤其是有BKVAN高危因素者，要考虑到BKVAN的可能。而BKVAN的临床及病理表现与急性排斥反应相似，免疫组织化学方法或电镜可以鉴别。正确的、适量的减少免疫抑制剂强度治疗BKVAN效果好，相反可加快BKVAN的进展。

Objective To determine the incidence of BK virus associated nephropathy（BKVAN） in renal-transplantation recipients, observe its histological features. Methods A total of 137 renal allograft biopsy specimens collected at our hospital during December 1999 to January 2008 were analyzed by routine histologic examination, immunohistochemistry and transmission electron microscopy （TEM） to screen for BKV. The case records of involved recipients were accessed to know their clinical manifestations, diagnostic characteristic and treatment regimens at that time. And the 1-, 3-year graft survival rate were analyzed by Kaplan-Meier analysis. Results A total of 16 renal biopsy specimens （ 11.7% ） were positive for BKV. Viral particales on the size of 35 - 40 nm were seen in the tubular epithelial cells of 3 biopsy specimens and 7 urinary sediment samples. The numbers of BKVAN recipients suffering acute rejection, using ALG/ATG/ OKT3 and using FKS06 ＋ MMF immunosuppressive protocol were 7, 7 and 10 respectively. In 14 cases of BKVAN, there was an elevated level of serum creatine concentrations. Four cases lost their grafts after using a large dose of immunosuppressives. And renal functions improved by a reduction of immunosuppression or a replacement of FKS06 with CsA in 8 cases. And graft functions deteriorated or had already failed in the remaining 4 cases whose immunosuppressive protocol were not changed. The 1-, 3-year graft survival rates were 81.3% and 54. 2% in BKVAN recipients respectively. Conclusion The diagnosis of BKVAN should be considered in recipients when their graft functions are deteriorating, especially for those with the accompanied risk factors. The morphological hallmarks of BKVAN are similar to those of acute rejection. The differentiation may be made by either immunohistochemistry or TEM. A proper modification of maintenance immunosuppression is effective in slowing down the progression of BKVAN.